ANIMAL MODELS: ATTEMPTS TO RELATE SUSTAINED ALTERATIONS
IN ANESTHETIC POTENCY WITH NEUROCHEMICAL COMPOSITION
One approach to the mechanism of anesthetic action is to relate
alterations in the anesthetic requirement with biochemical and biophysical changes
occurring in the CNS. A correlation between changes in the anesthetic requirement
and a structural change in the nervous system may indicate the critical properties
of the anesthetic site of action and how anesthetics affect that site.
Dietary Studies
Mice fed diets of different fatty acid composition (saturated
versus unsaturated) from birth have large alterations in certain synaptic membrane
fatty acid components.[158]
The most notable changes
occur in the synaptic membrane phosphatidylethanolamine and phosphatidylserine fractions
in mice fed the saturated-fat diet; these mice exhibit a relative decrease in docosahexaenoic
(22:6ω3) and an increase in eicosatrienoic (20:3ω9) fatty acids. However,
these alterations in synaptic membrane fatty acid composition have little or no influence
on the righting-reflex ED50
for nitrous oxide and isoflurane.[158]
In contrast, diet-induced alterations in rat brain fatty acid composition have been
correlated with modest alterations in anesthetic potency.[159]
Compared with rats on a control diet, rats maintained on a fat-free diet exhibit
lower levels of whole-brain arachidonic acid (20:4ω6) and docosahexaenoic acid
and an increase in eicosatrienoic acid. The fat-deprived animals exhibited a 10%
to 33% decrease in MAC for methoxyflurane, halothane, isoflurane, and cyclopropane
compared with control rats.[159]
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